Oxazoline-derived tridentate N, N, N-ligand as well as synthesis method and application thereof

Abstract

The invention belongs to the field of organic chemical ligands, and particularly discloses an oxazoline-derived tridentate N, N, N-ligand and a synthesis method and application thereof.Chiral oxazoline and quinoline sulfonamide are used as core frameworks, the tridentate N, N, N-ligand of a novel structure is developed, the ligand is shown in the general formula (I), and the structural formula (I) is shown in the description. The specific compound shown in the general formula (I) is successfully applied to the asymmetric catalytic reaction. The novel chiral ligand has abundant structural characteristics, induces excellent enantioselectivity, and can be widely applied to three-dimensional convergent free radical asymmetric cross-coupling reaction of tertiary halogenated alkane and (hetero) arylamine. The method has important guiding significance for developing a novel catalytic system to solve other types of three-dimensional convergent free radical asymmetric reactions.

Description

Technical Field

[0001] This invention belongs to the field of organic chemical ligands, and specifically discloses an oxazoline-derived tridentate N,N,N-ligand, its synthesis method, and its uses. Background Technology

[0002] Chiral oxazoline skeletons are not only widely found in biologically active molecules, but also serve as an important class of chiral ligands in various transition metal-catalyzed asymmetric reactions in organic asymmetric synthesis. Currently, the most common chiral oxazoline ligands in asymmetric catalysis are dialkyl-substituted bisoxazoline ligands (Box ligands) and C2-symmetric bisoxazoline pyridine ligands (PyBox ligands). These chiral ligands can only modulate the stereoselectivity of the reaction by forming coordinate bonds with transition metals.

[0003] In recent years, with the development of transition metal-catalyzed radical asymmetric chemistry, the demand for various novel chiral ligands has been increasing. Anionic ligands, due to their ability to directly bond with transition metals, possess numerous advantages. First, they can significantly enhance the reducing power of transition metals, enabling them to undergo single-electron transfer reactions with haloalkanes to generate alkyl radical species. Second, anionic ligands can also solve the problem of transition metal poisoning, thus addressing some challenges that neutral ligands cannot solve. Therefore, the design and synthesis of novel anionic ligands has become a current research hotspot. Cinchona bark-derived N,N,N(P)- anionic ligands have been successfully applied to copper-catalyzed radical asymmetric cross-coupling reactions, bifunctionalization reactions of alkenes, and oxidative asymmetric coupling reactions of C-H bonds. However, due to the diversity of radical antitypes, we need to further develop more types of chiral anionic ligands to provide specific steric environments for catalytic reactions, thereby achieving the goal of more catalytic asymmetric reactions. Summary of the Invention

[0004] To address the problems existing in the prior art, the first aspect of this invention proposes an oxazoline-derived tridentate N,N,N-ligand...

[0005] The body is shown in general formula (Ⅰ):

[0006]

[0007] Among them, R 1 Selected from hydrogen and alkyl groups;

[0008] R 2 Selected from hydrogen, alkyl, alkoxy, and halogen;

[0009] The k is selected from any integer from 0 to 4;

[0010] R 3 Selected from hydrogen and alkyl groups;

[0011] R 4 Selected from hydrogen, alkyl, carbocyclic, monocyclic phenyl, and fused-ring aryl groups;

[0012] R 5 Selected from hydrogen, alkyl, and phenyl;

[0013] In some specific embodiments of the first aspect of the present invention, the R 1 Selected from C1 to C4 alkyl groups.

[0014] In some specific embodiments of the first aspect of the present invention, the R 2 Selected from methoxy, wherein k is selected from 1 or 2, or, wherein R 2 Selected from fluorine, or, said R 2 Selected from alkyl groups, wherein the H on the alkyl group is optionally R a Instead, the R a Selected from F.

[0015] In some specific embodiments of the first aspect of the present invention, the R 4 Selected from alkyl, carbocyclic, and monocyclic phenyl groups, wherein R 4 Any H is R b Instead, the R b Selected from C1-C3 alkyl, halogen, and monocyclic aryl groups.

[0016] In some specific embodiments of the first aspect of the present invention, the R 5 R 3 Selected from alkyl groups, wherein R 5 R 3 The atoms bonded to them together form a ring Ar, wherein the ring Ar is selected from 3- to 7-membered heterocyclic groups and C1- to C6 carbocyclic groups, and the ring Ar is fused with an aryl group, as shown in the structural formula.

[0017] A second aspect of the present invention provides a specific form of the ligand described in the first aspect, comprising the following compounds:

[0018]

[0019]

[0020] A third aspect of this invention provides a method for preparing the ligands described in the first and second aspects, comprising the following steps: in the presence of EDCI and DMAP, compound S1 and compound S2 react as follows:

[0021]

[0022] Compound S1 and compound S2 react to give intermediate S3;

[0023] Intermediate S3 reacts with compound S4 to yield an oxazoline-derived tridentate N,N,N-ligand;

[0024] R 1 R 2 R 3 R 4 R 5 As defined in the first aspect.

[0025] The fourth aspect of this invention proposes the application of the ligand described in the first aspect in the stereopolymeric radical asymmetric cross-coupling reaction of tertiary haloalkanes and (hetero)aromatic amines.

[0026] In some specific embodiments of the fourth aspect of the present invention, the application is specifically as follows: under an inert atmosphere, the oxazoline-derived tridentate N,N,N-ligand described in any one of the first aspects is mixed with CuI and Cs2CO3, and then an organic solution including tertiary chloroalkanes and 3,5-ditrifluoromethylaniline is added to obtain compound (A).

[0027]

[0028] The R 6 R 7 Each is independently selected from alkyl, carbocyclic, monocyclic phenyl, and fused-ring aryl groups;

[0029] In some specific embodiments of the fourth aspect of the present invention, the R 6 Selected from ethyl, R 7 Selected from monocyclic aryl groups.

[0030] In some specific embodiments of the fourth aspect of the present invention, the organic solution is selected from 1,4-dioxane.

[0031] In some specific embodiments of the fourth aspect of the present invention, the inert atmosphere is an argon atmosphere.

[0032] In some specific embodiments of the fourth aspect of the present invention, the application is carried out at room temperature.

[0033] In this invention, "room temperature" refers to 40–5°C in some embodiments, 35–10°C in some embodiments, 30–15°C in some embodiments, 25–20°C in some embodiments, and 20°C in some embodiments.

[0034] The term "alkyl" refers to a monovalent straight-chain or branched saturated hydrocarbon group, such as methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, tert-butyl, pentyl, hexyl, etc.

[0035] The term "carbocyclic (group)" refers to a saturated or partially unsaturated monocyclic or polycyclic cyclic hydrocarbon group, which may contain 3 to 20 carbon atoms, preferably 3 to 12 (e.g., 3, 4, 5, 6, 7, 8, 9, 10, 11, 12) carbon atoms, and more preferably 3 to 6 carbon atoms. The partially unsaturated monocyclic or polycyclic cyclic hydrocarbon group is a saturated cycloalkyl group or may optionally contain one, two, or more double and / or triple bonds on its ring, thereby forming a so-called cycloalkenyl or cycloynyl group.

[0036] Unless otherwise stated, all chemicals were purchased commercially available and did not undergo further purification. Solvents such as dichloromethane and tetrahydrofuran used in the experiments were anhydrous. Thin-layer chromatography (TLC) was performed using 60F254 silica gel plates. Silica gel column chromatography was performed using Qingdao marine silica gel (particle size 0.040-0.063 mm). TLC development was performed using UV light (254 nm) or iodine. NMR spectra were characterized using a Bruker DPX 400 nuclear magnetic resonance instrument. 1 ¹H NMR was performed at 400 MHz using deuterated chloroform as the solvent and tetramethylsilane (TMS) as an internal standard. Chemical shifts are expressed in ppm, and coupling constants are expressed in Hz. 1 In H NMR, δ represents chemical shift, s represents singlet, d represents doublet, t represents triplet, q represents quartet, p represents quintet, and m represents multiplet.

[0037] Advantages of the invention:

[0038] This invention develops a novel class of tridentate N,N,N-ligands with chiral oxazolines and quinoline sulfonamides as the core framework, and has successfully applied them to asymmetric catalytic reactions. These novel chiral ligands possess rich structural features; the electronic and steric effects of the substituents in the chiral oxazolines and quinoline sulfonamides can be tuned, thereby inducing excellent enantioselectivity. The ligands of this invention can be widely applied not only to stereo-aggregate radical asymmetric cross-coupling reactions of tertiary haloalkanes and (hetero)aromatic amines, but also provide important guidance for developing novel catalytic systems to solve other types of stereo-aggregate radical asymmetric reactions. Detailed Implementation

[0039] General Synthetic Methods for Ligands

[0040]

[0041] General Step 1: Compound S1 (10 mmol), compound S2 (15–30 mmol, preferably 15 mmol), and anhydrous zinc chloride (20–40 mmol, preferably 30 mmol) are placed in a 50 mL round-bottom flask, purged with argon three times, and 20 mL of chlorobenzene is added. The mixture is then stirred at 120–140 °C (preferably 130 °C) for 24–72 hours, monitored by TLC, until compound S1 is completely eliminated. Post-treatment: After cooling to room temperature, water and ethyl acetate are added, followed by 1 mL of ethylenediamine and stirring until the system is completely clear. The mixture is then extracted with ethyl acetate, the organic layer is separated, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue is then subjected to silica gel column chromatography to give intermediate S3 (40–90% yield).

[0042] General Step 2: Intermediate S3 (5 mmol), compound S4 (5–10 mmol, preferably 7.5 mmol), and DMAP (0.5–1.5 mmol, preferably 1 mmol) are placed in a 50 mL round-bottom flask, purged three times with argon gas, and pyridine (15–50 mL, preferably 25 mL) is added. The mixture is then stirred at room temperature for 24 hours, quenched with water, and the organic layer is separated. The mixture is dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue is purified by silica gel column chromatography to give the product (60–99% yield).

[0043] Examples 1-25 were prepared using general steps 1 and 2:

[0044] Example 1

[0045]

[0046] Characterization data of ligand 1:

[0047] 1 H NMR (400MHz, CDCl3) δ12.73(s,1H),8.58–8.56(m,1H),8.36–8.34(m,1H),8.09–8.07(m,1H),7.97–7.95(m,1H),7.81–7.75(m,2H),7.6 0–7.56(m,1H),7.40–7.25(m,7H),6.94–6.90(m,1H),5.56(dd,J=10.1,7.9Hz,1H),4.71(dd,J=10.1,8.4Hz,1H),4.20(t,J=8.2Hz,1H). 13C NMR (100MHz, CDCl3) δ163.9,151.3,143.6,142.0,139.5,136.3,135.9,133.7,132.4,13 2.0,129.5,128.8,128.6,127.7,126.8,125.0,121.9,121.4,116.4,112.8,73.4,70.0.

[0048] Example 2

[0049]

[0050] Characterization data of ligand 2:

[0051] 1 H NMR(400MHz, CDCl3)δ12.86(s,1H),9.01–9.00(m,1H),8.34–8.31(m,2H) ,8.11–8.08(m,1H),7.98–7.96(m,1H),7.72–7.67(m,1H),7.59–7.55(m,2 H),7.43–7.40(m,1H),7.23–7.19(m,1H),4.30–4.22(m,1H),4.22–4.13( m,2H),1.86–1.74(m,1H),1.73–1.63(m,1H),0.91(td,J=7.4,1.3Hz,3H).

[0052] Example 3

[0053]

[0054] Characterization data of ligand 3:

[0055] 1 H NMR (400MHz, CDCl3) δ12.95(s,1H),8.95–8.94(m,1H),8.60–8.57(m,1H),8.15–8.12(m ,1H),7.99–7.96(m,1H),7.70–7.65(m,2H),7.61–7.57(m,1H),7.45–7.42(m,1H),7.25– 7.21(m,1H),6.89–6.85(m,1H),4.37(dd,J=9.6,8.2Hz,1H),4.25–4.19(m,1H),4.04(t, J=8.2Hz, 1H), 1.96–1.84 (m, J=6.7Hz, 1H), 1.21 (d, J=6.7Hz, 3H), 1.00 (d, J=6.8Hz, 3H). 13C NMR (100MHz, CDCl3) δ162.6,151.0,143.8,139.3,136.3,136.2,133.7,132.3,132 .0,129.1,128.7,125.1,122.0,121.2,116.2,112.9,72.8,69.4,33.4,19.1,18.6.

[0056] Example 4

[0057]

[0058] Characterization data of ligand 4:

[0059] 1 H NMR (400MHz, CDCl3) δ12.87(s,1H),8.93–8.92(m,1H),8.56–8.54(m,1H),8.12–8. 10(m,1H),7.96–7.94(m,1H),7.71–7.65(m,2H),7.58–7.54(m,1H),7.43–7.40(m, 1H),7.26–7.20(m,1H),6.88–6.84(m,1H),4.49–4.43(m,1H),4.37(t,J=9.0Hz,1H ), 4.03(t,J=8.2Hz,1H),1.74–1.67(m,1H),1.59–1.28(m,8H),0.99–0.91(m,6H). 13 C NMR (100MHz, CDCl3) δ162.5,150.9,143.8,139.3,136.4,136.1,133.6,132.1,131.8,129.1,1 28.7,125.0,121.9,121.2,116.3,113.0,69.6,69.5,42.2,32.3,32.2,20.1,19.6,14.5,14.4.

[0060] Example 5

[0061]

[0062] Characterization data of ligand 5:

[0063] 1H NMR(400MHz, CDCl3)δ12.81(s,1H),8.96–8.95(m,1H),8.59–8.57(m,1H),8.16–8.13(m, 1H),8.00–7.97(m,1H),7.71–7.65(m,2H),7.62–7.58(m,1H),7.46–7.43(m,1H),7.25–7. 21(m,1H),6.89–6.85(m,1H),4.53–4.41(m,2H),3.91(t,J=7.4Hz,1H),2.04–1.91(m,1H) ,1.83(dt,J=13.7,6.9Hz,1H), 1.45(dt,J=13.8,6.9Hz,1H), 1.07(dd,J=6.6,1.4Hz,6H). 13 C NMR (100MHz, CDCl3) δ162.5,151.0,143.8,139.3,136.4,136.2,133.7,132.3,132 .0,129.2,128.8,125.1,122.0,121.3,116.4,113.2,71.9,65.2,45.4,25.8,22.8.

[0064] Example 6

[0065]

[0066] Characterization data of ligand 6:

[0067] 1 H NMR(400MHz, CDCl3)δ12.92(s,1H),8.99–8.98(m,1H),8.58–8.56(m,2H),8. 13–8.11(m,1H),7.96–7.93(m,1H),7.70–7.66(m,1H),7.59–7.55(m,2H),7.4 4–7.42(m,1H),7.23–7.20(m,1H),4.26(dd,J=11.2,9.6Hz,1H),4.20(dd,J= 12.4,10.2Hz,1H),4.05–4.01(m,1H),1.66–1.56(m,2H),1.56–1.31(m,10H).

[0068] Example 7

[0069]

[0070] Characterization data of ligand 7:

[0071] 1H NMR(400MHz, CDCl3)δ12.68(s,1H),9.02–9.01(m,1H),8.60–8.58(m,2H),8.11–8.0 9(m,1H),7.86–7.84(m,1H),7.73–7.69(m,1H),7.55–7.52(m,2H),7.46–7.43(m,1H ),7.24–7.22(m,1H),4.29(dd,J=12.1,3.2Hz,1H),4.18(dd,J=12.1,5.4Hz,1H),4. 09–4.03(m,1H),1H),2.07–1.99(m,1H),1H),1.78–1.62(m,2H),1.61–1.45(m,6H).

[0072] Example 8

[0073]

[0074] Characterization data of ligand 8:

[0075] 1 H NMR(400MHz, CDCl3)δ12.96(s,1H),8.97–8.96(m,1H),8.61–8.59(m,1H),8.16–8.14(m,1H),8.00–7.98(m,1H),7.69–7 .66(m,2H),7.63–7.59(m,1H),7.46–7.43(m,1H),7.27–7.23(m,1H),6.91–6.87(m,1H),4.33–4.14(m,3H),1.06(s,9H). 13 C NMR (100MHz, CDCl3) δ162.7,151.1,143.9,139.5,136.7,136.2,133.7,132.2,1 32.0,129.2,128.8,125.1,122.0,121.2,116.2,112.8,76.2,67.6,33.9,25.9.

[0076] Example 9

[0077]

[0078] Characterization data of ligand 9:

[0079] 1H NMR(400MHz, CDCl3)δ12.77(s,1H),8.95–8.89(m,1H),8.62–8.58(m,1H),8.17–8.14(m,1H),8.00–7.97(m,1H),7.75–7.61(m,3H),7 .48–7.22(m,7H),6.89–6.84(m,1H),4.73–4.70(m,1H),4.31–4.29(m,1H),4.09–4.05(m,1H),3.38–3.34(m,1H),2.81–2.78(m,1H). 13 C NMR (100MHz, CDCl3) δ163.2,151.0,143.8,139.3,137.7,136.3,136.2,133.8,132.4,132. 2,129.4,129.3,128.8,128.7,126.7,125.2,122.0,121.4,116.3,113.0,70.5,68.1,41.8.

[0080] Example 10

[0081]

[0082] Characterization data of ligand 10:

[0083] 1 H NMR(400MHz, CDCl3)δ12.66(s,1H),8.59–8.56(m,1H),8.45–8.44(m,1H), 8.11–8.09(m,1H),7.99–7.96(m,1H),7.80–7.74(m,2H),7.61–7.57(m,1H ),7.32–7.27(m,4H),7.08–7.02(m,2H),6.94–6.90(m,1H),5.55(dd,J=10 .1,7.9Hz,1H),4.71(dd,J=10.1,8.4Hz,1H),4.13(dd,J=12.5,3.1Hz,1H). 13 C NMR (100MHz, CDCl3) δ164.0,162.2(d,J=244.6Hz),151.1,143.6,139.4,137.8(d,J=3.2Hz),136.2,136.1,133.8,1 32.5, 132.1, 129.5, 128.7, 128.3 (d, J = 8.0Hz), 125.0, 121.9, 121.4, 116.4, 115.6 (d, J = 21.2Hz), 112.7, 73.4, 69.2.19 F NMR (376MHz, CDCl3) δ-114.75.

[0084] Example 11

[0085]

[0086] Characterization data of ligand 11:

[0087] 1 H NMR(400MHz, CDCl3)δ12.62(s,1H),8.62–8.61(m,1H),8.53–8.52(m,1H),8.09– 8.06(m,1H),7.94–7.92(m,1H),7.72–7.70(m,1H),7.59–7.49(m,4H),7.45–7.4 3(m,2H),7.35–7.29(m,5H),7.25–7.21(m,3H),6.82(t,J=7.6Hz,1H),5.18(q,J =8.9Hz, 1H), 4.39 (t, J = 9.2Hz, 1H), 4.23 (d, J = 8.1Hz, 1H), 4.02 (t, J = 8.9Hz, 1H). 13 C NMR (400MHz, CDCl3) δ163.5,150.9,143.8,141.6,141.4,139.4,136.4,136.0,133.6,132.1,129.2,12 9.0,128.8,128.70,128.69,128.5,126.8,126.5,125.0,121.9,121.2,116.4,112.9,70.6,70.2,56.2.

[0088] Example 12

[0089]

[0090] Characterization data of ligand 12:

[0091] 1H NMR (400MHz, CDCl3) δ12.93(s,1H),8.87–8.86(m,1H),8.60–8.58(m,1H),7.88–7.78(m,6H),7.63–7.61(m,1H),7.54–7.50(m,1H),7.46– 7.41(m,3H),7.37–7.32(m,2H),7.19–7.16(m,1H),6.97–6.93(m,1H),6.05(t,J=9.4Hz,1H),4.85(t,J=9.3Hz,1H),4.00(t,J=8.5Hz,1H). 13 C NMR (100MHz, CDCl3) δ164.2,151.6,143.6,139.6,137.7,136.1,135.6,133.8,133.7,132.4,132.1,130.2,12 9.5,128.8,128.5,127.9,126.2,125.7,125.6,124.8,123.5,122.4,121.9,121.4,116.6,112.8,73.1,66.9.

[0092] Example 13

[0093]

[0094] Characterization data of ligand 13:

[0095] 1 H NMR(400MHz, CDCl3)δ12.65(s,1H),8.54–8.52(m,1H),8.30–8.29(m,1H),8.03 –8.00(m,1H),7.91–7.88(m,1H),7.74–7.72(m,1H),7.65–7.61(m,2H),7.54–7. 50(m,1H),7.35–7.22(m,4H),7.18–7.13(m,1H),6.82–6.79(m,1H),5.89(d,J= 7.9Hz, 1H), 5.42–5.35 (m, 1H), 3.50 (dd, J = 18.0, 6.9Hz, 1H), 3.33–3.28 (m, 1H). 13C NMR (100MHz, CDCl3) δ163.0,151.1,143.6,141.6,139.6,139.1,135.9,135.8,133.7,132.4,132. 0,129.3,128.6,128.5,127.6,126.0,125.2,124.9,121.9,121.3,116.3,113.1,81.8,76.7,39.5.

[0096] Example 14

[0097]

[0098] Characterization data of ligand 14:

[0099] 1 H NMR(400MHz, CDCl3)δ12.78(s,1H),8.62–8.60(m,1H),8.53–8.52(m,1H),8.13–8.10(m,1H),8.01–7.98(m,1H),7.93–7.90 (m,1H),7.88–7.85(m,1H),7.64–7.60(m,1H),7.38–7.33(m,1H),7.32–7.28(m,1H),7.07–6.89(m,11H),5.95–5.87(m,2H). 13 C NMR (100MHz, CDCl3) δ164.3,151.4,143.7,139.8,137.2,136.5,136.03,135.97,133.7,132.6,132. 0,129.6,128.7,127.9,127.7,127.6,127.1,126.4,125.1,122.0,121.5,116.7,112.7,84.1,74.4.

[0100] Example 15

[0101]

[0102] Characterization data of ligand 15:

[0103] 1H NMR(400MHz, CDCl3)δ11.27(s,1H),8.70–8.68(m,1H),8.51–8.49(m,1H) ,8.11–8.09(m,1H),7.95–7.92(m,1H),7.57–7.52(m,2H),7.41–7.30(m, 6H), 7.11 (t, J = 8.0Hz, 1H), 6.78 (d, J = 7.6Hz, 1H), 5.46 (dd, J = 10.3, 8.9Hz, 1H), 4.66 (dd, J = 10.3, 8.5Hz, 1H), 4.17 (t, J = 8.7Hz, 1H), 2.36 (s, 3H). 13 C NMR (100MHz, CDCl3) δ164.3,151.1,143.5,141.7,139.3,138.2,136.3,136.2,133.6,131. 7,130.7,128.8,128.6,127.6,126.6,125.7,125.1,122.0,116.2,116.1,73.8,69.3,22.2.

[0104] Example 16

[0105]

[0106] Characterization data of ligand 16:

[0107] 1 H NMR(400MHz, CDCl3)δ12.63(s,1H),8.57–8.54(m,1H),8.50–8.48(m,1H),8.13–8.11(m,1H),8.00–7.98(m,1H),7.62–7.55(m,2H),7.4 2–7.31(m,6H),7.26–7.18(m,1H),6.69–6.64(m,1H),5.54(dd,J=10.4,8.5Hz,1H),4.78(dd,J=10.3,8.5Hz,1H),4.27(t,J=8.6Hz,1H). 13C NMR (100MHz, CDCl3) δ162.4 (d, J = 2.7Hz), 161.9 (d, J = 255.8Hz), 151.3, 143.5, 141.5, 140.6 (d, J = 4.4Hz), 136.2, 135.9, 133.9, 132.7 (d, J=11.2Hz),132.2,128.8,128.7,127.8,126.7,125.1,122.1,112.7(d,J=3.2Hz),109.8(d,J=22.7Hz),103.2(d,J=13.6Hz),74.1,68.6. 19 F NMR (376MHz, CDCl3) δ-105.87.

[0108] Example 17

[0109]

[0110] Characterization data of ligand 17:

[0111] 1 H NMR(400MHz, CDCl3)δ12.32(s,1H),8.54–8.52(m,1H),8.40–8.38(m,1H), 8.10–8.08(m,1H),7.97–7.94(m,1H),7.77(d,J=9.2Hz,1H),7.59–7.55(m ,1H),7.40–7.26(m,7H),6.88(dd,J=9.2,3.1Hz,1H),5.52(dd,J=10.1,8. 0Hz, 1H), 4.69 (dd, J = 10.1, 8.4Hz, 1H), 4.19 (t, J = 8.3Hz, 1H), 3.71 (s, 3H). 13 C NMR (100MHz, CDCl3) δ163.6,154.1,151.2,143.7,141.9,136.4,136.0,133.6,133.0,132. 0,128.8,128.6,127.7,126.7,125.0,121.9,118.9,118.5,114.0,113.5,73.5,70.1,55.5.

[0112] Example 18

[0113]

[0114] Characterization data of ligand 18:

[0115] 1H NMR(400MHz, CDCl3)δ12.57(s,1H),9.03–9.02(m,1H),8.34–8.26(m,2H),8.07–8.05(m,1H),7.70–7.67(m,1H),7.53–7.51(m,1H),7.40–7.31 (m,5H),7.29–7.25(m,1H),7.12(s,1H),5.60–5.55(m,1H),4.45(dd,J=12.5,3.1Hz,1H),4.35(dd,J=12.4,5.0Hz,1H),3.89(d,J=10.8Hz,4H). 13 C NMR (100MHz, CDCl3) δ162.9,151.0,146.6,145.1,141.6,140.4,136.3,134.9,134.5,131.1,1 30.3,128.7,128.1,127.9,127.0,125.4,123.1,118.1,110.6,105.9,75.8,70.2,56.3,56.1.

[0116] Example 19

[0117]

[0118] Characterization data of ligand 19:

[0119] 1 H NMR(400MHz, CDCl3)δ11.72(s,1H),8.86–8.84(m,1H),8.48–8.46(m,1H),8.16–8 .14(m,1H),8.00–7.98(m,1H),7.64–7.58(m,2H),7.39–7.36(m,1H),7.34–7.32(m ,2H),7.30–7.28(m,1H),7.25–7.22(m,2H),7.20–7.14(m,1H),7.11–7.06(m,1H), 5.21(dd,J=10.2,8.7Hz,1H), 4.66(dd,J=10.2,8.3Hz,1H), 4.08(t,J=8.5Hz,1H). 19 F NMR (376MHz, CDCl3) δ-115.17.

[0120] Example 20

[0121]

[0122] Characterization data of ligand 20:

[0123] 1 H NMR(400MHz, CDCl3)δ12.92(s,1H),8.57–8.55(m,1H),8.30–8.28(m,1H),8.11–8.09(m,1H),8.00–7.98(m,1H),7.77–7.73(m,1H),7.6 5–7.55(m,2H),7.40–7.25(m,6H),6.63–6.58(m,1H),5.55(dd,J=10.1,7.8Hz,1H),4.71(dd,J=10.1,8.4Hz,1H),4.20(t,J=8.1Hz,1H). 13 C NMR (100MHz, CDCl3) δ164.8(d,J=249.7Hz),163.3,151.4,143.5,141.9,141.5(d,J=11.9Hz),136.0,135.9,133.9,132.0,131.5(d ,J=10.4Hz),128.8,128.7,127.7,126.8,125.1,122.0,109.0(d,J=2.9Hz),108.6(d,J=22.1Hz),103.9(d,J=28.1Hz),73.4,69.9. 19 FNMR (376MHz, CDCl3) δ-104.11.

[0124] Example 21

[0125]

[0126] Characterization data of ligand 21:

[0127] 1 H NMR (400MHz, CDCl3) δ12.84(s,1H),8.59–8.57(m,1H),8.29–8.28(m,1H),8.15–8.09(m,2H),7.99(d,J=8.2Hz,1H),7.86(d,J=8.2H z,1H),7.62–7.58(m,1H),7.46–7.23(m,6H),7.16–7.14(m,1H),5.59(t,J=9.0Hz,1H),4.76(t,J=9.3Hz,1H),4.24(t,J=8.1Hz,1H). 13C NMR (100MHz, CDCl3) δ163.0,151.3,143.5,141.5,139.9,136.1,135.7,134.1,133.7(q,J=32.5Hz),132.1,130.1,12 8.9,128.7,127.8,126.7,125.0,123.3(q,J=271.4Hz),122.0,117.8–117.7(m),115.4,113.5–113.4(m),73.7,70.0. 19 F NMR (376MHz, CDCl3) δ-63.35.

[0128] Example 22

[0129]

[0130] Characterization data of ligand 22:

[0131] 1 H NMR(400MHz, CDCl3)δ11.43(s,1H),8.80–8.78(m,1H),8.55–8.53(m,1H),8. 13–8.10(m,1H),7.98–7.92(m,2H),7.84–7.76(m,3H),7.61–7.49(m,5H),7. 34(dd,J=8.3,4.3Hz,1H),7.15(t,J=8.0Hz,1H),6.84–6.81(m,1H),6.12(t, J=9.8Hz, 1H), 4.91 (dd, J=10.5, 8.3Hz, 1H), 4.09–4.05 (m, 1H), 2.38 (s, 3H).

[0132] Example 23

[0133]

[0134] Characterization data of ligand 23:

[0135] 1H NMR (400MHz, CDCl3) δ12.40(s,1H),8.58–8.55(m,1H),7.98(d,J=8.4Hz,1H),7.95–7.92(m,1H),7.80–7.78(m,1H),7.69(d,J=8.5Hz,1H),7.54(t, J=7.7Hz,1H),7.37–7.25(m,7H),6.95–6.91(m,1H),5.52(dd,J=10.1,8.0 Hz, 1H), 4.71 (dd, J = 10.1, 8.4Hz, 1H), 4.20 (t, J = 8.2Hz, 1H), 2.46 (s, 3H). 13 C NMR (100MHz, CDCl3) δ164.2,160.8,143.4,141.7,139.6,135.93,135.86,133.4,132.3,131. 9,129.5,128.8,127.7,127.0,126.5,124.2,123.0,121.3,116.8,113.0,73.6,670.0,25.3.

[0136] Example 24

[0137]

[0138] Characterization data of ligand 24:

[0139] 1 H NMR (400MHz, CDCl3) δ12.52(s,1H),8.57(d,J=7.3Hz,1H),7.93(d,J=8.4Hz,1H),7.88 (d,J=8.1Hz,1H),7.67–7.63(m,2H),7.49(t,J=7.8Hz,1H),7.34–7.33(m,4H),7.24–7. 19(m,3H),6.83(t,J=7.6Hz,1H),4.64(p,J=7.5Hz,1H),4.29(t,J=8.9Hz,1H),4.05(t, J=8.1Hz, 1H), 3.21 (dd, J=13.7, 6.1Hz, 1H), 2.78 (dd, J=13.6, 7.6Hz, 1H), 2.55 (s, 3H). 13C NMR (100MHz, CDCl3) δ163.1,160.5,143.3,139.3,137.6,135.9,135.4,133.4,132.1,132.0,1 29.3,129.3,128.6,126.9,126.5,124.0,122.9,121.0,116.0,112.7,70.4,68.1,41.7,25.3.

[0140] Example 25

[0141]

[0142] Characterization data of ligand 25:

[0143] 1 H NMR (400MHz, CDCl3) δ12.42(s,1H),8.52(d,J=7.3Hz,1H),7.91–7.84(m,2H),7.67–7.60(m,2H),7.48–7.41(m,3H),7.38–7.31(m,6H),7.24 –7.16(m,4H),6.80(t,J=7.6Hz,1H),5.10(q,J=8.8Hz,1H),4.39(t,J=9.2Hz,1H),4.17(d,J=8.6Hz,1H),4.01(t,J=8.7Hz,1H),2.36(s,3H). 13 C NMR (100MHz, CDCl3) δ163.4,160.6,143.4,141.4,141.3,139.5,135.8,135.5,133.3,132.1,129.3,128. 9,128.8,128.6,128.5,126.9,126.8,126.6,124.0,122.9,120.9,116.1,112.6,70.8,70.1,56.5,25.1.

[0144] Example 26

[0145] The ligands of this invention are applied to stereopolymeric radical asymmetric cross-coupling reactions of tertiary haloalkanes and aromatic amines.

[0146]

[0147] CuI (cuprous iodide, 10 mol% equivalent), ligand L1 (15 mol% equivalent), and Cs₂CO₃ (cesium carbonate, 3.0 equivalent) were added to a Schlenk tube equipped with a magnetic stir bar and dried in an oven. Argon gas was purged three times, followed by the addition of a tertiary chloroalkane (0.2 mmol), 3,5-ditrifluoromethylaniline (0.24 mmol), and 1,4-dioxane (1,4-dioxane, 4.0 mL). The reaction was then carried out at room temperature for 72 h. After the reaction was complete (monitored by TLC), the precipitate was filtered off and washed with ethyl acetate. The solution was then evaporated and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 7.5 / 1) to give the product in 92% yield and 80% ee.

[0148] Characterization data of the product: It is a white solid, [α]D 27 = +21 (c 2.2, CHCl3). HPLC conditions: Chiralcel IG (n-hexane / isopropanol = 98 / 2, flow rate 1.0 mL / min, λ = 254 nm), t R (major) = 9.30 min, t R (minor) = 11.23 min. 1 H NMR (400MHz, CDCl3) δ7.49–7.48(m,2H),7.41–7.38(m,2H),7.32–7.28(m,1H),7.00(s,1H),6.86(s,2H),6.76 (s,1H),3.70–3.01(m,8H),2.68(dq,J=14.6,7.4Hz,1H),2.32(dq,J=14.2,7.2Hz,1H),0.89(t,J=7.3Hz,3H). 13 C NMR (100MHz, CDCl3) δ170.1, 145.1, 140.6, 131.9 (q, J = 32.4Hz), 129.2, 128.2, 126.8, 1 23.4(q,J=271.0Hz),113.43–113.39(m),109.8–109.7(m),66.1,66.0,45.7,23.8,8.1. 19 F NMR (376MHz, CDCl3) δ -63.34. HRMS (ESI) m / z precise mass calculation C 22 H 23 F6N2O2[M+H] + 461.1658, measured value 461.1653.

[0149]

[0150] The reaction results of existing ligands La to Lh with the ligands of the present invention are shown in the table below (L1 represents the ligand of Example 1, and so on):

[0151] The reaction results are shown in the table below (L1 represents the ligand of Example 1, and so on):

[0152]

[0153]

[0154] It is evident that, in the stereopolymeric radical asymmetric cross-coupling reaction of tertiary haloalkanes and aromatic amines, the ligands of this invention exhibit advantages over existing ligands in both stereoselectivity and reaction efficiency. Therefore, designing novel multidentate anionic ligands can realize a wider range of asymmetric reactions.

[0155] The above description is merely a specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any variations or substitutions that can be easily conceived by those skilled in the art within the technical scope disclosed in the present invention should be included within the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be determined by the scope of the claims.

Claims

1. An oxazoline-derived tridentate N,N,N-ligand, as shown in general formula (Ⅰ): in, R 1 Selected from hydrogen and alkyl groups; R 2 Selected from hydrogen, alkyl, alkoxy, and halogen; The k is selected from any integer from 0 to 4; R 3 Selected from hydrogen and alkyl groups; R 4 Selected from hydrogen, alkyl, carbocyclic, monocyclic aryl, and fused-ring aryl; R 5 Selected from hydrogen, alkyl, and phenyl.

2. The oxazoline-derived tridentate N,N,N-ligand according to claim 1, characterized in that, The R 1 Selected from C1 to C4 alkyl groups.

3. The oxazoline-derived tridentate N,N,N-ligand according to claim 2, characterized in that, The R 2 Selected from methoxy, wherein k is selected from 1 or 2, or, wherein R 2 Selected from F, or, said R 2 Selected from alkyl groups, wherein the H on the alkyl group is optionally R a Instead, the R a Selected from F.

4. The oxazoline-derived tridentate N,N,N-ligand according to claim 1, characterized in that, The R 4 Selected from alkyl, carbocyclic, and monocyclic phenyl groups, wherein R 4 Any H is R b Instead, the R b Selected from C1-C3 alkyl, halogen, and monocyclic aryl groups.

5. The oxazoline-derived tridentate N,N,N-ligand according to claim 4, characterized in that, The R 5 R 3 The atoms bonded to them together form a ring Ar, wherein the ring Ar is selected from C3-C6 carbon cyclic groups, and / or the ring Ar is fused with an aryl group, as shown in the structural formula.

6. An oxazoline-derived tridentate N,N,N-ligand selected from the following compounds:

7. A method for preparing the oxazoline-derived tridentate N,N,N-ligand according to any one of claims 1 to 6, characterized in that, The reaction includes the following steps: In the presence of EDCI and DMAP, compounds S1 and S2 react as follows: Compound S1 and compound S2 react to give intermediate S3; Intermediate S3 reacts with compound S4 to yield an oxazoline-derived tridentate N,N,N-ligand; R 1 R 2 R 3 R 4 R 5 As described in claim 1.

8. The use of the oxazoline-derived tridentate N,N,N-ligand according to any one of claims 1 to 7 in the stereopolymeric radical asymmetric cross-coupling reaction of tertiary haloalkanes and (hetero)aromatic amines.

9. The application according to claim 8, specifically, under an inert atmosphere, the oxazoline-derived tridentate N,N,N-ligand according to any one of claims 1 to 7 is mixed with CuI and Cs2CO3, and then an organic solution including tertiary chloroalkanes and 3,5-ditrifluoromethylaniline is added to obtain compound (A); The R 6 R 7 Each is independently selected from alkyl, carbocyclic, monocyclic phenyl, and fused-ring aryl groups.

10. The application according to claim 9, wherein the R 6 Selected from ethyl, R 7 The organic solvent is selected from monocyclic aryl groups, and / or the organic solution is selected from 1,4-dioxane, and / or the inert atmosphere is argon, and / or the application is carried out at room temperature.

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